Friedrich Oliver, Fink Rainer H A, von Wegner Frederic
Medical Biophysics, Institute of Physiology & Pathophysiology, University of Heidelberg, INF 326, 69120, Heidelberg, Germany.
School of Biomedical Sciences, University of Queensland, St. Lucia, 4072, Brisbane, QLD, Australia.
Biophys Rev. 2010 Feb;2(1):29-38. doi: 10.1007/s12551-009-0027-2. Epub 2009 Dec 18.
Skeletal muscle is a highly organized tissue that has to be optimized for fast signalling events conveying electrical excitation to contractile response. The site of electro-chemico-mechanical coupling is the skeletal muscle triad where two membrane systems, the extracellular t-tubules and the intracellular sarcoplasmic reticulum, come into very close contact. Structure fits function here and the signalling proteins DHPR and RyR1 were the first to be discovered to bridge this gap in a conformational coupling arrangement. Since then, however, new proteins and more signalling cascades have been identified just in the last decade, adding more diversity and fine tuning to the regulation of excitation-contraction coupling (ECC) and control over Ca store content. The concept of Ca entry into working skeletal muscle has become attractive again with the experimental evidence summarized in this review. Store-operated Ca entry (SOCE), excitation-coupled Ca entry (ECCE), action-potential-activated Ca current (APACC), and retrograde EC-coupling (ECC) are new concepts additional to the conventional orthograde ECC; they have provided fascinating new insights into muscle physiology. In this review, we discuss the discovery of these pathways, their potential roles, and the signalling proteins involved that show that the triad may become a crowded place in time.
骨骼肌是一种高度组织化的组织，必须针对将电兴奋传递至收缩反应的快速信号事件进行优化。电化学机械偶联的位点是骨骼肌三联体，其中两个膜系统，即细胞外横小管和细胞内肌浆网，紧密接触。这里结构与功能相匹配，信号蛋白二氢吡啶受体（DHPR）和兰尼碱受体1（RyR1）是最早被发现以构象偶联方式连接这一间隙的蛋白。然而，从那时起，仅在过去十年中就发现了新的蛋白和更多的信号级联反应，为兴奋 - 收缩偶联（ECC）的调节以及对钙储存含量的控制增加了更多的多样性和精细调节。随着本综述中总结的实验证据，钙进入工作骨骼肌的概念再次变得具有吸引力。储存式钙内流（SOCE）、兴奋偶联钙内流（ECCE）、动作电位激活钙电流（APACC）和逆行兴奋 - 收缩偶联（ECC）是传统顺行ECC之外的新概念；它们为肌肉生理学提供了迷人的新见解。在本综述中，我们讨论了这些途径的发现、它们的潜在作用以及涉及的信号蛋白，这些表明三联体可能很快会变得拥挤不堪。
